Teresa Løvold Berents

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient‐reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient‐reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient‐reported symptoms were discussed [including the Patient‐Oriented SCOring Atopic Dermatitis index, Patient‐Oriented Eczema Measure (POEM), Self‐Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient‐reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Can early skin care normalise dry skin and possibly prevent atopic eczema? A pilot study in young infants

BACKGROUND Atopic eczema (AE) affects approximately 20% of children in Northern countries. Onset during early infancy is common and is characterised by altered skin barrier, increased water loss and defective lipid layer. Restoration of skin barrier by emollients and/or oil baths is an important part of AE treatment, but its role in preventing xerosis and AE is unknown. The present pilot study aimed to assess if xerosis, and possibly AE, could be reduced at six months of age by early introduction of frequent oil baths/facial fat cream in infants with dry skin. METHODS A controlled intervention pilot study included 56 six-week-old infants with xerosis, but not AE. Skin quality score ranging from 0 (normal skin) to 4 (probable AE), was assessed at inclusion, three and six months of age, with skin quality at six months as main outcome. One well baby clinic was recruited for intervention, frequent skin care (oil bath (0.5 dl) and facial fat cream, five well baby clinics recruited for observation only. RESULTS The intervention group (n=24) had more often normal skin (75%) at six months than the observation group (37.5%) (p<0.001), and less often probable AE (4.0 vs. 19.0%, respectively, ns). Oil baths were performed regularly, 2-4 up to 5-7 times/week in the intervention group, vs. fewer oil baths with sparse volume of oil in the observation group. No adverse reactions were reported. CONCLUSION Regular oil baths in infants seem to reduce xerosis and may possibly reduce atopic eczema.

Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis

Contact sensitization is common and affects up to 20% of the general population. The clinical manifestation of contact sensitization is allergic contact dermatitis. This is a clinical expression that is sometimes difficult to distinguish from other types of dermatitis, for example irritant and atopic dermatitis. Several studies have examined the pathogenesis and severity of allergic contact dermatitis by measuring the absence or presence of various biomarkers. In this review, we provide a non‐systematic overview of biomarkers that have been studied in allergic contact dermatitis. These include genetic variations and mutations, inflammatory mediators, alarmins, proteases, immunoproteomics, lipids, natural moisturizing factors, tight junctions, and antimicrobial peptides. We conclude that, despite the enormous amount of data, convincing specific biomarkers for allergic contact dermatitis are yet to be described.

Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial

BACKGROUND Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence-based guidelines, it is often justified by the belief in a subgroup effect in individuals developing atopic disease. We aimed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction, atopic eczema, or allergic sensitisation. METHODS In the randomised, double-blind, multicentre Bronchiolitis ALL trial, 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay. Randomisation was done centrally, and the two study medications (20 mg/mL racemic epinephrine or 0.9% saline) were prepared in identical bottles. The dose given depended on the infants weight: 0.10 mL, less than 5 kg; 0.15 mL, 5-6.9 kg; 0.2 mL, 7-9.9 kg; and 0.25 mL, 10 kg or more; all dissolved in 2 mL of 0.9% saline before nebulisation. The primary outcome was the length of hospital stay. In this follow-up study, 294 children were reinvestigated at 2 years of age with an interview, a clinical examination, and a skin prick test for 17 allergens, determining bronchial obstruction, atopic eczema, and allergic sensitisation, on which subgroup analyses were done. Analyses were done by intention to treat. The trial has been completed and is registered at ClinicalTrials.gov (number NCT00817466) and EUDRACT (number 2009-012667-34). FINDINGS Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years (143 [48.6%] of 294 patients; p(interaction)=0.40). However, the presence of atopic eczema or allergic sensitisation by the age of 2 years (n=77) significantly interacted with the treatment effect of inhaled epinephrine (p(interaction)=0.02); the length of stay (mean 80.3 h, 95% CI 72.8-87.9) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years (-19.9 h, -33.1 to -6.3; p=0.003). No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years (+16.2 h, -11.0 to 43.3; p=0.24). INTERPRETATION Contrary to our hypothesis, hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema, allergic sensitisation, or recurrent bronchial obstruction. The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases. FUNDING Medicines for Children Network, Norway.

Skin Barrier Function and Staphylococcus aureus Colonization in Vestibulum Nasi and Fauces in Healthy Infants and Infants with Eczema: A Population-Based Cohort Study

Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants.

Vitamin D levels and atopic eczema in infancy and early childhood in Norway: a cohort study.

Epidemiological data and the effect of sun exposure on atopic eczema (AE) suggest that vitamin D (vitD) may be involved in the pathogenesis.

Transepidermal water loss in infancy associated with atopic eczema at 2 years of age: a population‐based cohort study

DEAR EDITOR, Skin barrier function can be evaluated by measuring transepidermal water loss (TEWL). High TEWL is found in children with atopic eczema and in infants with a mutation in the gene encoding profilaggrin, a precursor of filaggrin, which is an important protein for skin barrier function. In a recent study by Kelleher et al., high TEWL at 2 days and 2 months preceded and predicted atopic eczema at 1 year of age, independently of parental atopy and filaggrin mutation status. Using a cohort of infants living in south-east Norway, we aimed to investigate whether TEWL in infants without atopic eczema was associated with atopic eczema at 2 years of age. Ethical approval and informed consent were obtained. The children, recruited from the general population in the cities of Oslo and Fredrikstad, were examined at two visits at a mean age of 6 0 months (min,max 1 2–13 4) and 24 0 months (min,max 17 5–35 2), respectively, within the period 2012– 2014 (Table 1). Maternal or paternal atopy was defined as reports of atopic eczema, asthma or allergic rhinitis by the respective parent. Atopic eczema was diagnosed clinically by experienced physicians based on the criteria of Hanifin and Rajka or on a history of physician-diagnosed atopic eczema. Children with a rash that did not fulfil these criteria were classified as having a rash. Infants with atopic eczema at the first visit were excluded from the study cohort. TEWL was measured on the lateral part of one upper arm, using an open chamber DermaLab USB (Cortex, Hadsund, Denmark) system. The infants, wearing a nappy only, were acclimatized for a minimum of 15 min under standardized environmental conditions of a temperature of 20–25 °C, in line with studies by Kelleher et al., and 20–50% humidity. TEWL measurements performed while the infants were crying were not included. TEWL was reported as the mean of three consecutive measurements. Data on TEWL measurements performed under the required conditions at the first visit and on atopic eczema at the second visit were obtained in 116 of the 196 children (59%) whose characteristics are shown in Table 1. The median TEWL at the first visit was 7 95 g m 2 h 1 (Q1,Q3; 5 51, 10 21). Using the area under the receiver operating characteristic curve, the optimal cut-off value for TEWL was calculated to be 9 33 g m 2 h , defining low and high TEWL in the analyses. At the second visit atopic eczema was diagnosed in 19 of 116 children (16%). Analysing the association between high TEWL at the first visit and atopic eczema at the second visit, Hosmer and Lemeshow’s step-down procedure was performed to adjust for potential confounding variables, that is, paternal or maternal atopy, paternal or maternal ethnicity, parental income, infants’ sex, age, filaggrin mutation, weight for length, vitamin D level and having a rash at the first visit, as well as the season when the first visit was made and the relative ambient humidity, leaving only high TEWL and having a rash in the final model (Table 2). Table 1 Infants without atopic eczema (n = 196) at the first visit, with and without transepidermal water loss (TEWL) data at the first visit or data on atopic eczema at the second visit. Data are presented as numbers (%) unless otherwise stated